0099-2399/90/1602-0085/$02.00/0 JOURNAL OF ENDOOONT~CS Copyr,ght 9 1990 by The American Association of EndocIont~sts
Pr,nted m U S A
VOL
16. NO
2. FfBRUARV 1990
Treating Acute Pain: Do's and Don'ts, Pros and Cons Stephen A. Cooper, DMD, PhD
The mechanisms of action of centrally and peripherally acting analgesics are reviewed. Therapeutic implications are cited.
mechanisms of pain in detail, a brief summary is appropriatc to establish a framework for categorizing the armamentarium of analgesic agents (1-3). When cells are destroyed, the intracellular material is dumped into the surrounding microcosm. With normal ccl luar turnover, the debris is metabohzed and transported away via the vascular system. When there is tissue injury, so many cells are destroyed in a localized area that the normally innocuous substances build up to a level in which they become transmitters for the activation of pain and inflammation. Free nervc endings in the area of injury serve as the afferent pain receptors. When there are sufficient numbers of these receptors activated over an area (spatial summation) and over time (temporal summation), the pain message is amplified, carried Io the spinal column via the afferent nerves, and ultimately transmitted to the brain for an appropriate response. At the same time pain receptors are activated, the same local chemical mediators are recruiting cells to initiate the inflammatory process in the area of injury. Those local mediators most closely associated w~th pain and inflammation are bradykinin, histamine, and prostagiandins. Bradykinm is a polypeplide that exists as an inactive kininogen precursor in blood. When tissue injury occurs, it is quickly converted to bradykimn by the en/yme kallikrein and is integrally involved in fast onset, sharp pain, and local vasodilation. Histamine also exists in storage form as part of mast cells and once activated, it is involved in the local vascular changes initiating the inflammatory response. The prostaglandins are metabolic products of the ruptured cell membrane. They are produced through a cascade of chemical reactions originating with the membrane fatty acid known as arachidonic acid. The prostaglandins appear to amplify both the pain and inflammatory, response and they are continually being metabolized as long as tissue debris is present. As the biochemical mediators build in the injured tissue, more and more pain impulses reach the central nervous system (CNS). In the spinal column, at the level of the dorsal horn, the transmitter known as substance P is released and this activates the spinal pain pathways leading to the brain. As spinal activity is initiated through the specialized spinal pain pathways (neo- and paleo-spinollhalamic tracts), the sympathetic system of the autonomic nervous system also is being activated. Thus. "'fright. flight, and fight" becomes an integral part of the pain process and a major contributor to the overall emotional response of the patient. Under normal, nonpainful conditions, the spinal column is busy integrating millions of afferent impulses ranging from temperature to propioception. It appears that fast-conducting, nonpainful impulses that enter the dorsal horn actually inhibit
Pain is a malady that crosses almost every medical discipline. It frequently overwhelms the original disease and becomes the major focus of treatment. [n dentistry, pain often is the primary motivator that brings people to the office. Because pain is such a complex physiological, biochemical, and psychological phenomenon, its diagnosis and treatment also can be very complex. Too often in both medicine and dentistry a haphazard or shotgun approach ts used to treat pain and too little attention is devoted to a systematic matching of the treatment to both the pain state and the patient's state of mind. There is no area o f medicine that can rely on just one drug to cure a medical condition and, certainly, pain is not the exception. Inadequate treatment of pain results in patients ha~ ing unnecessa~ suffering and encourages self-experimentation from the medicine cabinet, l h e converse, using an elephant gun to shoot a mouse, will relieve the pain but at the expense of exposing patients to potentially serious side effects. Because of the complexity of pain, there is no computer program that can print out the most appropriate analgesic for every patient. Prescribing the "best" analgesic therapy requires that the clinician have knowledge of the pharmacology of drugs, the psychological profile of the patient, and an ability to make a damage assessment of the area causing the pain. This review will briefly summarize the biochemical and physiologJcal basis of pain and attempt to develop a rational pharmacological approach for treating a vanety of dental pain situations. The reader should appreciate that some generalizations are made concerning mechanisms to avoid getting overwhelmed with detail. The major emphasis of this review will focus on the clinical management of pain.
REVIEW O F PAIN M E C l i A N I S M S Most pain episodes are initiated by injury to tissue. Dentists performing surgery are literally mashing millions of cells; likewise, a periapical abscess does its damage by destroying cells in the periapical area of a tooth. The body's natural reaction to this trauma is to protect itself locally from further tissue destruction, while at the same time alerting the brain of the impending danger. Although various texts cover the 85
86
Cooper
the release of substance P. Carrying this one step further, the gate control theory of Melzack and Wall postulates that distractors such as rubbing or pressing near a painful area may activate these fast-tract impulses and assist in suppressing the painful stimuli at the level of substance P release (4). In fact, dentists often use these distractor techniques to lessen the pain from injection. Once the brain receives the pain impulses, the body is alerted and reactions from appropriate to hysterical can ensue. If the brain becomes overwhelmed with pain, syncope can occur to temporarily reduce the system to minimal survival activity. Most commonly, the brain tells the body to protect itself from further injury, assess the environmental situation, and then plan appropriate exogenous treatment. The brain takes its own action by releasing transmitters called endorphins and enkephalins. These endogenous peptides activate descending nueronal tracts in the spinal column that find their way back to the substance P terminals in the dorsal horn and inhibit the further release of substance P. In addition to the endogenous peptides, serotonin receptors appear to be involved in these descending loops. Thus, as the brain receives pain impulses and recognizes danger, the system attempts to automatically down regulate the flow of the afferent pain impulses to the brain. P H A R M A C O I , O G I C A L A P P R O A C t l E S TO PAIN CONTROL The pain system as described above offers many opportunities for pharmacological intervention. However, one must appreciate that there can be a large gap between a chemical intervention and an acceptable therapeutic treatment. Some approaches to breaking the "pain chain" are still investigational while others are the mainstay of analgesic therapy. There are two major groups of drugs used systemically to treat pain (Fig. 1). The first group works at the site of injury and is best described as the peripherally acting analgesics (PAs). The second group works in the brain and is best described as the centrally acting analgesics (CAs). P E R I P H E R A L L Y ACI'ING ANALGESICS At the level of tissue injury, the obvious approach is to inhibit the local mediators of pain and inflammation. At present, inhibiting the metabolism of arachidonic acid to prostaglandins (PGs) appears to be the most effective mechanism. Antihistamines are not useful as analgesics, and bradykinin antagonists are just being developed. The PA analgesic~ work by blocking the cyclo-oxygenase enzyme that converts aa to PGs. The classical cyclo-oxygenase inhibitor is aspirin. Table 1 summarizes the other drugs in this category. Sometimes these drugs are referred to as nonsteroidal anti-inflammatory drugs (NSAIDs). However, it is preferable to subclassify NSAIDs into those with analgesic indications and those that are only indicated for more serious inflammatory diseases such as rheumatoid arthritis or ankylosing spondylitis. This latter group has a higher incidence of serious side effects. The ultimate clinical indications are determined by the Food and Drug Administration and are based on the onset of effect, duration of action and therapeutic
Journal of Endodontics
CENTRALLY-ACTING ANALGESICS
LOCAL AGENTS
~;PERIPHERALLYACTING ANALGESICS
FIG 1. Mechanism of action for analgesic agents.
index (safety). As can be seen from Table 1, several agents have both analgesic and other anti-inflammatory actions. The most commonly used PA analgesics are aspirin, acetaminophen, ~ ibuprofen, naproxen sodium (Anaprox), and diflunisal (Dolobid). Others with analgesic indications include fenoprofen (Nalfon), ketoprofen (Orudis), meclofenamate sodium (Meclomen), and mefanamic acid (Ponstel). The PA analgesics have two major limitations. They have a plateau effect beyond which more drug provides no additional analgesia. Therelore, the very best PA analgesics do not have indications for severe pain and most have only limited use for moderately severe pain. Their other limitation relates to side effects. Most notable are gastrointestinal irritation in about 10% of the population and, in a very small group, clinically significant bleeding due to inhibition of platelet aggregation. About 10 to 20% of asthmatics have a sensitivity to PAs that could result in an asthmatic attack. Acetaminophen is the only agent in this group that does not have the side effect limitations; however, it only has weak anti-inflammatory activity. The gastrointestinal effects are due, in part, to inhibiting the prostaglandin system in the gut that normally coats the stomach lining. The irritation is greatly potentiated and can result in internal hemorrhaging when these drugs are mixed with alcohol. All of the PAs have antipyretic effects due to their central inhibition of the cyclo-oxygenase enzyme. In some clinical situations, this effect can present a problem by masking the fever caused by infection. Infrequently, these drugs cause tinnitus at therapeutic dosages (Table 2). The therapeutic index of this group is relatively high and rarely do patients reach toxic blood levels when these drugs are prescribed for acute analgesia. The PAs (except for acetaminophen) would be contraindicated in patients with ulcers or a history of tinnitus and in asthmatics with a history of sensitivity. As with any chemical, a true allergic reaction also may occur. In ranking the PAs according to efficacy, the propionic acid derivatives are more effective analgesics than aspirin or acetaminophen. With intense pain, this difference becomes more clinically relevant. Meclofenamate sodium also appears to be in the efficacy range of ibuprofen; whereas diflunisal is best known for its long duration of action. From a clinical perspective, when treating acute pain, time to onset and peak effect are more critical than duration of effect. However, there may be some advantage in having a drug with a sufficiently long duration to carry the patient through the night. Distinct advantages of the PAs are that they are not scheduled by the 1 For the purposes of this review, acetaminophen is being classified as a PA analgesic.
Vol. 16, No. 2, February 1990
Treating Acute Pain
87
TABLE 1. Currently available PAs (NSAID)
Drug Name
Trade Name
Chemical Derivation
Indication
OTC/RX
Type Pain
Aspirin
Many
Salicylate
PA*, AA
OTC
Mild
Acetaminophen
Many
Amino-phenol
PA
OTC
Mild
Diflunisal
Dolobid
Salicylate
PA, AA
Rx
Mild-moderate
Ibuprofen
Propionic acid
PA, AA
OTC/Rx
Mild-moderate
Naproxen sodium
Motrin, Rufen Advil, Nuprin Anaprox
Propionic acid
PA, AA
Rx
Mild-moderate
Ketoprofen
Orudis
Propionic acid
PA, AA
Rx
Mild-moderate
Fenoprofen
Nalfon
Propionic acid
PA, AA
Rx
Mild-moderate
Meclofenamate sodium
Meclomen
Fenamate
PA. AA
Rx
Mild-moderate
Mefenamic acid
Ponstel
Fenamate
PA, AA
Rx
Mild-moderate
Naproxen
Naprosyn
Propionic acid
PA, AA
Rx
Mild-moderate
Indomethacin Sulindac Piroxicam
Indocin Clinodl Feldene
Tolmetin
Tolecttn
Phenylbutazone
Butazolidin
Indole Indene Oxicam Pyrrole Pyrazolone
AA AA AA AA AA
Rx Rx Rx Rx Rx
NA NA NA NA NA
Analgesic Dose Range (rag) (maximum/day) 325-1000 (4OO0) 325-1000 (4000) 250-1000 (1500) 200-400 (2400 Rx) 250-500 (1250) 25-75 (3OO) 200 (1200) 50-100
(400) 250-500 (1250) 250-500 (1250) NA NA NA NA NA
9 PA, analoes~c indication; AA, antiarttmtJc or otrter indications. NA. not a l ~ . a t ~ e
TABLE 2. Advantagee and limitations of PAs (NSAID)
Advantages Relief equivalent to narcotic combinations Minimal CNS side effects Favorable therapeutic index Several chemical classes Limitations Plateau of analgesic effect Gastrointestinal upset Inhibition of platelets "rinnitus Specific contraindications Ulcers Asthma Reye's syndrome Allergy
Drug Enforcement Agency (DEA) and they infrequently cause CNS side effects. CENTRALLY ACTING ANALGESICS Until pain impulses reach the brain, patients cannot recognize that trouble exists. People without pain recognition literally destroy their own bodies and rarely live through adolescence. More closely to home, dentists sometimes see the result of obliterating pain perception, when patients traumatize their tongue after local anesthetic injection. With normal pain perception, the brain quickly translates the pain message and the body reacts to remove itself from danger. When pain becomes pathological, it is possible to use drugs that work by altering the translation of the pain message at the level of the brain.
These CAs have no known therapeutic effects on the local mediators of pain nor on impulse transmission to the CNS; but they work at the level of the brain where the endogenous peptides are produced. It cannot be overemphasized that these are mood-altering drugs and many of their side effects are a direct result of their central mechanism of action (Table 3). The CA analgesics also are referred to as narcotic analgesics. With few exceptions, they are all scheduled drugs by the DEA. Drugs that arc chemically derived from opium are called opiates (e.g. morphine and codeine) and synthetic compounds that work like opium are called opioids (e.g. meperidine and propoxyphene). Another subclassificafion divides CAs into agonists and partial agonists. The partial agonists are represented by only four compounds and only pentazocine (Talwin) is available in an oral dosage form. The partial agonists are essentially similar to morphine unless the patient has a preexisting dependency to an agonist like morphine. In this situation, a drug like pentazocine will act as a reversal agent and precipitate an abstinence syndrome. From a dental standpoint, the partial agonists are of little use as analgesics. However, it is important to note that patients dependent on narcotic analgesics should not be given these agents. The CA analgesics present several clinical problems (Table 3). Most serious are their spectrum and high incidence of CNS side effects that include drowsiness, dizziness, euphoria, lightheadedness, and nausea. Unfortunately, these side effects are quite common at therapeutic doses. At higher dosages, they can cause respiratory depression and, on chronic administration, they can cause urinary retention and constipation. Only after prolonged administration, greater than 2 to 3 wk, does tolerance and dependency become an issue. This situation should not occur in treating acute dental pain.
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Cooper
The nausea caused by CA drugs is centrally mediated and usually limited to the first few doses. Once therapeutic blood levels are attained and maintained, the chemoreceptor trigger zone in the vomiting center becomes depressed and the nausea should not persist. Keeping patients in a quiet environment and in a reclining position during initial dosing should minimize the nausea. Another major drawback of the CA drugs is their "first pass effect" or liver metabolism. After oral administration, somewhere between 50 and 95% of opiate/opioid drugs arc metabolized to inactive metabolites in the liver on their very first pass from the gastrointestinal tract (Fig. 2). Since the liver sees the drug before the brain that means most of the orally administered dose never reaches the brain in an active lbrm. Because patients have both variable first pass efficiencies and brain receptor sensitivities, the clinical effects of these drugs by the oral route are unpredictable. One of the virtues of the CA analgesics is that they have no plateau effect. In clinical terms, this means more drug provides more pain relief with side effects being the limiting factor. For severe intractable pain, the CA analgesics still remain the drugs of choice especially by the more predictabl e injectable route. For most types of dental pain, single entity CA analgesics are not indicated. When a mood-altering drug is desired, one of the CA analgesics is generally combined with a PA analgesic. These fixed dose combinations are the most widely used analgesics in dentistry. The classic combinations consist of either aspirin or acetaminophen combined with codeine, hydrocodone, oxycodone, or propoxyphene. 2 Table 4 summarizes the CA analgesics according to chemical derivation and DEA schedule. Table 5 summarizes the available combinations of CAs with PAs. At present, none of the newer NSAIDs are available in combination with the CAs; however, several are in various stages of development.
Joumal of Endodontics TABLE 3. Advantages and limitations of CAs (narcotic)
Advantages Analgesic and mood-altering effects No plateau analgesic effect Limitations CNS side effects at therapeutic dosages Nausea Drowsiness I ightheadedness/dizziness Urinary retention Constipation Respiratory depression (at higher dosages) On chronic use Tolerance Dependence First pass liver metabolism Specific contraindications Allergy Cranial injuries (due to histamine release)
. - . . 9 ",,..
.
t
r
o.
-
FIG 2. The "first pass effect" of centrally acting analgesics.
CLINICAL USE OF ANALGESICS IN DENTISTRY The following remarks represent this author's philosophy of analgesic therapy. There may be other approaches that are as appropriate. The approach discussed emphasizes using analgesics with the greatest benefit/risk ratio with particular emphasis on minimizing the risk. For the most part, dental pain is treated on an outpatient basis, and the patients need to return to their daily routine almost immediately. Using drugs that depress psychomotor function when they are not indicated unnecessarily increases the risk factor. Acute dental pain is usually transient, rarely lasting more than 1 or 2 days. Pathological pain resulting from conditions such as pericornitis or an abscess should be relieved by dental treatment and acute postsurgical pain usually dissipates within a short time. The acute phase of pain can progress to a chronic phase with persistent edema and inflammation, but this phase generally is less intense and may require different analgesic therapy than the acute phase. Generally, the level of pain is correlated to both the length of surgery and the extent of violation to the periosteum. Thus, dental impaction surgery 2 Prpoxyphene is available either as the HCI salt or the napsylate salt. Propoxyphene napsylate (100 rag)is equivalentin active drug to propoxyphene
HC1(65rag).
is more painful than a simple tooth extraction or a single quadrant flap procedure. Figure 3 depicts a study comparing aspirin in two clinical situations; with the less traumatic extraction pain 650 mg of aspirin appears to be more effective than with impaction pain (5). It is important to assess pain from several perspectives before deciding on the appropriate analgesic. The following criteria are suggested: (a) the extent of the surgical procedure; (b) the psychological make-up of the patient; (c) the patient's past experience with analgesics; and (d) the planned activity of the patient over the next 24 to 48 h. For most dental pain situations, the PA analgesics are extremely effective (6-8). There is reasonable evidence that several of the newer NSAIDs are at least as effective as the traditional codeine combinations (8). If a patient can tolerate aspirin-like drugs, then ibuprofen, ketoprofen, naproxen sodium, or meclofenamate sodium at their maximum indicated dose will provide substantial analgesia without the narcotic side effects (Fig. 4). If the clinical situation permits, pretreatment with these agents will enhance their therapeutic effect (9, 10). However, the clinician needs to be cautious about the theoretical possibility of prolonged surgical bleeding. In the published pretreatment studies, this was not a problem. If a patient cannot tolerate aspirin-like drugs, then the only PA
Vol. 16, No. 2, February 1990
Treating Acute Pain
89
TABLE 4. Currently available CAs (narcotic)* Drug Name
Trade Name
Chemical Derivation
DEA Schedule
Dosage (mg)
Morphine Hydromorphone Codeine Hydrocodone Oxycodone Meperidine Methadone Propoxyphene
MS Contin Dilaudid NA NA NA Demerol Dolophine Darvon HCI Darvon Napsylate Talwin NX Stadol Nubain Buprenex
O :)late O ~iate O )iate O ~iate O 3iate O )ioid O ~ioid O :)ioid Opioid Partial agonist Partial agonist Partial agonist Partial agonist
It II II II II II II IV IV IV Rxt Rx V
30-60 1-4 15-60 NA NA 50-100 5-10 32-65 50-100 50 NA NA NA
Pentazocine Butorphanol Nalbuphine Buprenorphine
First Pass Metabolism Up to Up to Up to Up to Up to Up to Up to Up to Up to Up to Up to Up to NA
Dosage for Dental Use in Combinations
90% 90% 50% 50% 50% 90% 50% 50% 50% 95% 95% 95%
NRJ" NR 15-60 5-10 2.5-10 NR NR 32-65 50-100 NR NA NA NA
9 Several of these d~gs are indicated as oral analgesics only in com~natlon wi~ PAs. Single e n v y Oral CAs are not recommended fOr dental pain. 1" NR. not recommended; NA. not a.pplKT,al~e. ,1:Rx means avmlable by pteso'lption without DEA sdledulw'~g.
TABLE 5. Analgesic combinations used in dentistry Constituents Trade Name Tylenol w/Codeine #2
PAs
CAs
DEA Other
Ill
--
COD 30
--
1 tablet every 4 - 6 h
III
ASA 325
COD 15
--
III
ASA 325
COD 30
--
#4 Synalgos DC
ASA 325 ASA 356
COD 60 DHCOD 16
-CAF
Vicodin, Lortab, Zydone
ACET 500
HCOD 5-7.5
--
Percodan
ASA 325
OXCOD 5
--
Percodan-Demi
ASA 325
OXCOD 2.5
--
Tylox
ACET 500
OXCOD 5
--
Percocet
ACET 325
OXCOD 5
--
Darvocet-N 50 Darvocet-N 100 Darvon W/A.SA.w (HCI salt) Talwin Compound
ACET 650 ACET 650 ASA 325 ASA 325
PROPOX 50 PROPOX 100 PROPOX 65 PENTAZ 12.5
-----
Talacen Fiorinal w/Codeine #1 #2 #3
ACET 650
PENTAZ 25
--
2-3 tablets every 4-6 h 1-2 tablets every 4-6 h Not recommended1" 1-2 tablets every 4-6 h 1-2 tablets every 4-6 h 1-2 tablets every 4-6 h 1-2 tablets every 4-6 h 1-2 tablets every 4-6 h 1-2 tablets every 4-6 h 1 tablet every 4 - 6 h 1 tablet every 4-6 h 1 tablet every 4-6 h 2 tablets every 4-6 h 1 tablet every 4 - 6 h
ASA 325 ASA 325 ASA 325
COD 7.5 COD 15 COD 30
CAF 40, BUT 50 CAF 40, BUT 50 CAF 40, BUT 50
Not recommendedll Not recommended Not recommended
#4 (Empracet w/Codeine) (Phenaphen w/Codeine) Phenaphen 650 w/Codeine Empirin w/Codeine #2 #3
COD 15
--
ACET 300
COD 30
--
ACET 300
COD 60
ACET 650
Schedule
2-3 tablets every 4-6 h 1-2 tablets every 4-6 h Not recommended1
#3
ACET ~ 300
Recommended Dosage
III Ill
III III III III II~t II~t II~t
IV IV IV IV IV III III Ill
9 ACET. acetaminophefl: ASA, aspire; COD. codeine, HCOD. hydrOCXXtOne: OXCOD. oxycodone; DHCOD. dihydrocodelne; PROPOX. propoxyphef~ napsylate: PENTAZ. pentazocine: CAF. caffeine: BUT. b~JtaJbltal t # 4 Preparations are not recommended because they contain inadequate amounts of the PAs. use two #3s. -t In g e t , rat. tt~ use of DEA Sctledule II drugs is discouraged unless clearly indicated w Several other Oarvon preDaratio~'ls exist, e.g. Darvon Compo~.r I', This table is not all :nctustve end the not recommended cetegor~ ~s strictty the authors opinion.
90
Cooper
Joumal of Endodontics
alternative is aeetaminophen. Although an effective analgesic, it is a weaker anti-inflammatory drug and a less effective
analgesic than the propionic acid derivatives ( 11 ). Depending on the clinical situation, the lack of a moodaltering effect by the PAs can be an advantage or disadvantage. Certainly, there are clinical situations when the pain is so 6.0-
/
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E-
STUDY 17 / EXTRACTION PAIN / (N : 3 6 ) /
L,q v L,q W rr' 0
~J L~
w
L~.O
Z
uJ C~ L:J LL LL s >-
Z ud t--Z
( N : 7 ~ / "
8.0-
Z (3_
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N=IIO 0
325 6 0 1300 ASPIRIN DOSE IN mg FIG 3. Dose-response data for aspinn demonstrating the effect of different intensities of pain.
intense or when the patient's reaction to pain is so exaggerated that a mood-altering drug would be appropriate. In this situation, the clinician is dealing both with the quantitative and qualitative aspects of analgesia and centrally acting, moodaltering drugs may be most appropriate. The crux of the matter is that when the clinician deems it appropriate, the CAs are the drugs of choice to "buzz" the pain away. In dentistry, it is most beneficial to utilize the maximum effect of the PA analgesic and use the minimal amount of CA analgesic that will accomplish this goal. Table 5 lists the available combination analgesics and suggests the most rational dosage. Once the mood-altering effect is not needed, it is appropriate to switch therapy to the single entity PA analgesic. In most clinical situations, the need for a CA analgesic should not exceed 1 to 2 days. The clinician needs to be familiar with identity and amount of each constituent in the combination. In order to maximize the PA, it often is necessary to take more than one tablet of the combination or to take an extra acetaminophen, aspirin, or ibuprofen tablet along with the combination tablet. For example, it is better to take two acetaminophen (300 mg) with codeine (15 mg) tablets (two #2s) than one #3 tablet. Likewise, either three #2s or two #3s would be more efficacious than one #4 tablet. There also may be some benefit to alternating between an acetaminophen-codeine combination and ibuprofen (or other NSAID) every 2 to 3 h. Although lacking direct clinical support, this regimen offers the theoretical advantages of the anti-inflammatory effects of the PA and the additive effects of the CA. When dental pain is mild to moderate, most patients do surprisingly well on the newer PA analgesics. Only when the pain becomes more intense or the psychological situation is such that a mood-altering drug is required are the CA anal-
3"
x PLACEBO o A600 Eg A 3 0 0 + 030
(n=39) ( n =4-4-)
-~ A 6 0 0
(n=41)
+
IBU
4- 0 6 0 4-00
(n=39)
(n=40)
LIJ 0
LILIJ IZ"
z
N=203 o
0
~
i
1
2
3
....
i
i
4
HOURS FIG 4. Time-effect curves for placebo, 600 mg of 8cetaminophen, 300 mg of acetaminophen + 30 mg of codeine, 600 mg of acetaminophen + 60 mg of codeine, and 400 mg of ibuprofen. Mean pain relief scores are plotted against time in hours.
Vol. 16, No. 2, February 1990
gesics indicated. Generally, the codeine or hydrocodone combinations are most effective and only on rare occasions would a DEA schedule II be necessary. An understanding of the etiology of pain and the mechanisms of actions of analgesics can truly lead to better clinical management of pain problems. In almost all dental pain situations, the patient's pain can be controlled with minimal risk and side effects from the therapy. Dr. Cooper is director of Pharmacology and Graduate Education, Departmerit of Oral Surgery and Pharmacolgy, University of Pennsylvama..(-;cho~ of Dental Medicine, Plliladelpl'lla, PA
Roferencea 1. Chapman CR. Bon~ca JJ. Current concepts--acute pain Kalamazoo, MI: Upjohn, A Scope Pul)hcat~n, 1983.
Treating Acute Pain
91
2. Cooper SA PharmacoE)gy and therapeutics in dentistry. 2nd ed.. Chap 21. St. Louis, CV Mosby, 1985 3. Fields HL. Pain New York: McGraw-HiU, 1987. 4. Melzack R (ed). Pain measurement and assessment. New York: Raven Press, 1985. 5. Cooper SA. Comparative analgesic efficaces of aspldn and acetan.noptlen. Arch Intern Meal 1981;141:282-5. 6. Cooper SA. The relative efficacy of ibuprofen in dental pain. Compen Contin Educ Dent 1986;7:578-97. 7. Forbes JA, Beaver Wl, White EH, White RW, Neilson GB, Shackle.ford RW. Diflunisal, a new oral analgesic with unusually long duration of action J Am Med Assoc 1982:248:2139-42. 8. Cooper SA. New penF~efa, y-actJng oral analgesics. Annu Rev Pharmacol Toxicol 1983;23:617 -47 9. Dionne RA, Cooper SA. Delaying the onset of postoperative dental pain by pretreatment with ibuprofen. Oral Surg Oral Meal Oral Patho11978;45:8516. 10. a,onne RA. Carnpceli P.A,Cooper SA, Ha, DL, Buckingham B. Suppression of postoperative pare by I~eOpecatlve administration of ibuprolen in comparison to placebo, acetam~nophen and acetaminophen plus codeine. J CSn Pharmacol 1983;23:37-43. 11. Cooper SA The relative eff~acy of ibuprofen in dental pain. Compen Contin Educ Dent 1986;7:578-97.
Pr,nted m U S A
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16. NO
2. FfBRUARV 1990
Treating Acute Pain: Do's and Don'ts, Pros and Cons Stephen A. Cooper, DMD, PhD
The mechanisms of action of centrally and peripherally acting analgesics are reviewed. Therapeutic implications are cited.
mechanisms of pain in detail, a brief summary is appropriatc to establish a framework for categorizing the armamentarium of analgesic agents (1-3). When cells are destroyed, the intracellular material is dumped into the surrounding microcosm. With normal ccl luar turnover, the debris is metabohzed and transported away via the vascular system. When there is tissue injury, so many cells are destroyed in a localized area that the normally innocuous substances build up to a level in which they become transmitters for the activation of pain and inflammation. Free nervc endings in the area of injury serve as the afferent pain receptors. When there are sufficient numbers of these receptors activated over an area (spatial summation) and over time (temporal summation), the pain message is amplified, carried Io the spinal column via the afferent nerves, and ultimately transmitted to the brain for an appropriate response. At the same time pain receptors are activated, the same local chemical mediators are recruiting cells to initiate the inflammatory process in the area of injury. Those local mediators most closely associated w~th pain and inflammation are bradykinin, histamine, and prostagiandins. Bradykinm is a polypeplide that exists as an inactive kininogen precursor in blood. When tissue injury occurs, it is quickly converted to bradykimn by the en/yme kallikrein and is integrally involved in fast onset, sharp pain, and local vasodilation. Histamine also exists in storage form as part of mast cells and once activated, it is involved in the local vascular changes initiating the inflammatory response. The prostaglandins are metabolic products of the ruptured cell membrane. They are produced through a cascade of chemical reactions originating with the membrane fatty acid known as arachidonic acid. The prostaglandins appear to amplify both the pain and inflammatory, response and they are continually being metabolized as long as tissue debris is present. As the biochemical mediators build in the injured tissue, more and more pain impulses reach the central nervous system (CNS). In the spinal column, at the level of the dorsal horn, the transmitter known as substance P is released and this activates the spinal pain pathways leading to the brain. As spinal activity is initiated through the specialized spinal pain pathways (neo- and paleo-spinollhalamic tracts), the sympathetic system of the autonomic nervous system also is being activated. Thus. "'fright. flight, and fight" becomes an integral part of the pain process and a major contributor to the overall emotional response of the patient. Under normal, nonpainful conditions, the spinal column is busy integrating millions of afferent impulses ranging from temperature to propioception. It appears that fast-conducting, nonpainful impulses that enter the dorsal horn actually inhibit
Pain is a malady that crosses almost every medical discipline. It frequently overwhelms the original disease and becomes the major focus of treatment. [n dentistry, pain often is the primary motivator that brings people to the office. Because pain is such a complex physiological, biochemical, and psychological phenomenon, its diagnosis and treatment also can be very complex. Too often in both medicine and dentistry a haphazard or shotgun approach ts used to treat pain and too little attention is devoted to a systematic matching of the treatment to both the pain state and the patient's state of mind. There is no area o f medicine that can rely on just one drug to cure a medical condition and, certainly, pain is not the exception. Inadequate treatment of pain results in patients ha~ ing unnecessa~ suffering and encourages self-experimentation from the medicine cabinet, l h e converse, using an elephant gun to shoot a mouse, will relieve the pain but at the expense of exposing patients to potentially serious side effects. Because of the complexity of pain, there is no computer program that can print out the most appropriate analgesic for every patient. Prescribing the "best" analgesic therapy requires that the clinician have knowledge of the pharmacology of drugs, the psychological profile of the patient, and an ability to make a damage assessment of the area causing the pain. This review will briefly summarize the biochemical and physiologJcal basis of pain and attempt to develop a rational pharmacological approach for treating a vanety of dental pain situations. The reader should appreciate that some generalizations are made concerning mechanisms to avoid getting overwhelmed with detail. The major emphasis of this review will focus on the clinical management of pain.
REVIEW O F PAIN M E C l i A N I S M S Most pain episodes are initiated by injury to tissue. Dentists performing surgery are literally mashing millions of cells; likewise, a periapical abscess does its damage by destroying cells in the periapical area of a tooth. The body's natural reaction to this trauma is to protect itself locally from further tissue destruction, while at the same time alerting the brain of the impending danger. Although various texts cover the 85
86
Cooper
the release of substance P. Carrying this one step further, the gate control theory of Melzack and Wall postulates that distractors such as rubbing or pressing near a painful area may activate these fast-tract impulses and assist in suppressing the painful stimuli at the level of substance P release (4). In fact, dentists often use these distractor techniques to lessen the pain from injection. Once the brain receives the pain impulses, the body is alerted and reactions from appropriate to hysterical can ensue. If the brain becomes overwhelmed with pain, syncope can occur to temporarily reduce the system to minimal survival activity. Most commonly, the brain tells the body to protect itself from further injury, assess the environmental situation, and then plan appropriate exogenous treatment. The brain takes its own action by releasing transmitters called endorphins and enkephalins. These endogenous peptides activate descending nueronal tracts in the spinal column that find their way back to the substance P terminals in the dorsal horn and inhibit the further release of substance P. In addition to the endogenous peptides, serotonin receptors appear to be involved in these descending loops. Thus, as the brain receives pain impulses and recognizes danger, the system attempts to automatically down regulate the flow of the afferent pain impulses to the brain. P H A R M A C O I , O G I C A L A P P R O A C t l E S TO PAIN CONTROL The pain system as described above offers many opportunities for pharmacological intervention. However, one must appreciate that there can be a large gap between a chemical intervention and an acceptable therapeutic treatment. Some approaches to breaking the "pain chain" are still investigational while others are the mainstay of analgesic therapy. There are two major groups of drugs used systemically to treat pain (Fig. 1). The first group works at the site of injury and is best described as the peripherally acting analgesics (PAs). The second group works in the brain and is best described as the centrally acting analgesics (CAs). P E R I P H E R A L L Y ACI'ING ANALGESICS At the level of tissue injury, the obvious approach is to inhibit the local mediators of pain and inflammation. At present, inhibiting the metabolism of arachidonic acid to prostaglandins (PGs) appears to be the most effective mechanism. Antihistamines are not useful as analgesics, and bradykinin antagonists are just being developed. The PA analgesic~ work by blocking the cyclo-oxygenase enzyme that converts aa to PGs. The classical cyclo-oxygenase inhibitor is aspirin. Table 1 summarizes the other drugs in this category. Sometimes these drugs are referred to as nonsteroidal anti-inflammatory drugs (NSAIDs). However, it is preferable to subclassify NSAIDs into those with analgesic indications and those that are only indicated for more serious inflammatory diseases such as rheumatoid arthritis or ankylosing spondylitis. This latter group has a higher incidence of serious side effects. The ultimate clinical indications are determined by the Food and Drug Administration and are based on the onset of effect, duration of action and therapeutic
Journal of Endodontics
CENTRALLY-ACTING ANALGESICS
LOCAL AGENTS
~;PERIPHERALLYACTING ANALGESICS
FIG 1. Mechanism of action for analgesic agents.
index (safety). As can be seen from Table 1, several agents have both analgesic and other anti-inflammatory actions. The most commonly used PA analgesics are aspirin, acetaminophen, ~ ibuprofen, naproxen sodium (Anaprox), and diflunisal (Dolobid). Others with analgesic indications include fenoprofen (Nalfon), ketoprofen (Orudis), meclofenamate sodium (Meclomen), and mefanamic acid (Ponstel). The PA analgesics have two major limitations. They have a plateau effect beyond which more drug provides no additional analgesia. Therelore, the very best PA analgesics do not have indications for severe pain and most have only limited use for moderately severe pain. Their other limitation relates to side effects. Most notable are gastrointestinal irritation in about 10% of the population and, in a very small group, clinically significant bleeding due to inhibition of platelet aggregation. About 10 to 20% of asthmatics have a sensitivity to PAs that could result in an asthmatic attack. Acetaminophen is the only agent in this group that does not have the side effect limitations; however, it only has weak anti-inflammatory activity. The gastrointestinal effects are due, in part, to inhibiting the prostaglandin system in the gut that normally coats the stomach lining. The irritation is greatly potentiated and can result in internal hemorrhaging when these drugs are mixed with alcohol. All of the PAs have antipyretic effects due to their central inhibition of the cyclo-oxygenase enzyme. In some clinical situations, this effect can present a problem by masking the fever caused by infection. Infrequently, these drugs cause tinnitus at therapeutic dosages (Table 2). The therapeutic index of this group is relatively high and rarely do patients reach toxic blood levels when these drugs are prescribed for acute analgesia. The PAs (except for acetaminophen) would be contraindicated in patients with ulcers or a history of tinnitus and in asthmatics with a history of sensitivity. As with any chemical, a true allergic reaction also may occur. In ranking the PAs according to efficacy, the propionic acid derivatives are more effective analgesics than aspirin or acetaminophen. With intense pain, this difference becomes more clinically relevant. Meclofenamate sodium also appears to be in the efficacy range of ibuprofen; whereas diflunisal is best known for its long duration of action. From a clinical perspective, when treating acute pain, time to onset and peak effect are more critical than duration of effect. However, there may be some advantage in having a drug with a sufficiently long duration to carry the patient through the night. Distinct advantages of the PAs are that they are not scheduled by the 1 For the purposes of this review, acetaminophen is being classified as a PA analgesic.
Vol. 16, No. 2, February 1990
Treating Acute Pain
87
TABLE 1. Currently available PAs (NSAID)
Drug Name
Trade Name
Chemical Derivation
Indication
OTC/RX
Type Pain
Aspirin
Many
Salicylate
PA*, AA
OTC
Mild
Acetaminophen
Many
Amino-phenol
PA
OTC
Mild
Diflunisal
Dolobid
Salicylate
PA, AA
Rx
Mild-moderate
Ibuprofen
Propionic acid
PA, AA
OTC/Rx
Mild-moderate
Naproxen sodium
Motrin, Rufen Advil, Nuprin Anaprox
Propionic acid
PA, AA
Rx
Mild-moderate
Ketoprofen
Orudis
Propionic acid
PA, AA
Rx
Mild-moderate
Fenoprofen
Nalfon
Propionic acid
PA, AA
Rx
Mild-moderate
Meclofenamate sodium
Meclomen
Fenamate
PA. AA
Rx
Mild-moderate
Mefenamic acid
Ponstel
Fenamate
PA, AA
Rx
Mild-moderate
Naproxen
Naprosyn
Propionic acid
PA, AA
Rx
Mild-moderate
Indomethacin Sulindac Piroxicam
Indocin Clinodl Feldene
Tolmetin
Tolecttn
Phenylbutazone
Butazolidin
Indole Indene Oxicam Pyrrole Pyrazolone
AA AA AA AA AA
Rx Rx Rx Rx Rx
NA NA NA NA NA
Analgesic Dose Range (rag) (maximum/day) 325-1000 (4OO0) 325-1000 (4000) 250-1000 (1500) 200-400 (2400 Rx) 250-500 (1250) 25-75 (3OO) 200 (1200) 50-100
(400) 250-500 (1250) 250-500 (1250) NA NA NA NA NA
9 PA, analoes~c indication; AA, antiarttmtJc or otrter indications. NA. not a l ~ . a t ~ e
TABLE 2. Advantagee and limitations of PAs (NSAID)
Advantages Relief equivalent to narcotic combinations Minimal CNS side effects Favorable therapeutic index Several chemical classes Limitations Plateau of analgesic effect Gastrointestinal upset Inhibition of platelets "rinnitus Specific contraindications Ulcers Asthma Reye's syndrome Allergy
Drug Enforcement Agency (DEA) and they infrequently cause CNS side effects. CENTRALLY ACTING ANALGESICS Until pain impulses reach the brain, patients cannot recognize that trouble exists. People without pain recognition literally destroy their own bodies and rarely live through adolescence. More closely to home, dentists sometimes see the result of obliterating pain perception, when patients traumatize their tongue after local anesthetic injection. With normal pain perception, the brain quickly translates the pain message and the body reacts to remove itself from danger. When pain becomes pathological, it is possible to use drugs that work by altering the translation of the pain message at the level of the brain.
These CAs have no known therapeutic effects on the local mediators of pain nor on impulse transmission to the CNS; but they work at the level of the brain where the endogenous peptides are produced. It cannot be overemphasized that these are mood-altering drugs and many of their side effects are a direct result of their central mechanism of action (Table 3). The CA analgesics also are referred to as narcotic analgesics. With few exceptions, they are all scheduled drugs by the DEA. Drugs that arc chemically derived from opium are called opiates (e.g. morphine and codeine) and synthetic compounds that work like opium are called opioids (e.g. meperidine and propoxyphene). Another subclassificafion divides CAs into agonists and partial agonists. The partial agonists are represented by only four compounds and only pentazocine (Talwin) is available in an oral dosage form. The partial agonists are essentially similar to morphine unless the patient has a preexisting dependency to an agonist like morphine. In this situation, a drug like pentazocine will act as a reversal agent and precipitate an abstinence syndrome. From a dental standpoint, the partial agonists are of little use as analgesics. However, it is important to note that patients dependent on narcotic analgesics should not be given these agents. The CA analgesics present several clinical problems (Table 3). Most serious are their spectrum and high incidence of CNS side effects that include drowsiness, dizziness, euphoria, lightheadedness, and nausea. Unfortunately, these side effects are quite common at therapeutic doses. At higher dosages, they can cause respiratory depression and, on chronic administration, they can cause urinary retention and constipation. Only after prolonged administration, greater than 2 to 3 wk, does tolerance and dependency become an issue. This situation should not occur in treating acute dental pain.
88
Cooper
The nausea caused by CA drugs is centrally mediated and usually limited to the first few doses. Once therapeutic blood levels are attained and maintained, the chemoreceptor trigger zone in the vomiting center becomes depressed and the nausea should not persist. Keeping patients in a quiet environment and in a reclining position during initial dosing should minimize the nausea. Another major drawback of the CA drugs is their "first pass effect" or liver metabolism. After oral administration, somewhere between 50 and 95% of opiate/opioid drugs arc metabolized to inactive metabolites in the liver on their very first pass from the gastrointestinal tract (Fig. 2). Since the liver sees the drug before the brain that means most of the orally administered dose never reaches the brain in an active lbrm. Because patients have both variable first pass efficiencies and brain receptor sensitivities, the clinical effects of these drugs by the oral route are unpredictable. One of the virtues of the CA analgesics is that they have no plateau effect. In clinical terms, this means more drug provides more pain relief with side effects being the limiting factor. For severe intractable pain, the CA analgesics still remain the drugs of choice especially by the more predictabl e injectable route. For most types of dental pain, single entity CA analgesics are not indicated. When a mood-altering drug is desired, one of the CA analgesics is generally combined with a PA analgesic. These fixed dose combinations are the most widely used analgesics in dentistry. The classic combinations consist of either aspirin or acetaminophen combined with codeine, hydrocodone, oxycodone, or propoxyphene. 2 Table 4 summarizes the CA analgesics according to chemical derivation and DEA schedule. Table 5 summarizes the available combinations of CAs with PAs. At present, none of the newer NSAIDs are available in combination with the CAs; however, several are in various stages of development.
Joumal of Endodontics TABLE 3. Advantages and limitations of CAs (narcotic)
Advantages Analgesic and mood-altering effects No plateau analgesic effect Limitations CNS side effects at therapeutic dosages Nausea Drowsiness I ightheadedness/dizziness Urinary retention Constipation Respiratory depression (at higher dosages) On chronic use Tolerance Dependence First pass liver metabolism Specific contraindications Allergy Cranial injuries (due to histamine release)
. - . . 9 ",,..
.
t
r
o.
-
FIG 2. The "first pass effect" of centrally acting analgesics.
CLINICAL USE OF ANALGESICS IN DENTISTRY The following remarks represent this author's philosophy of analgesic therapy. There may be other approaches that are as appropriate. The approach discussed emphasizes using analgesics with the greatest benefit/risk ratio with particular emphasis on minimizing the risk. For the most part, dental pain is treated on an outpatient basis, and the patients need to return to their daily routine almost immediately. Using drugs that depress psychomotor function when they are not indicated unnecessarily increases the risk factor. Acute dental pain is usually transient, rarely lasting more than 1 or 2 days. Pathological pain resulting from conditions such as pericornitis or an abscess should be relieved by dental treatment and acute postsurgical pain usually dissipates within a short time. The acute phase of pain can progress to a chronic phase with persistent edema and inflammation, but this phase generally is less intense and may require different analgesic therapy than the acute phase. Generally, the level of pain is correlated to both the length of surgery and the extent of violation to the periosteum. Thus, dental impaction surgery 2 Prpoxyphene is available either as the HCI salt or the napsylate salt. Propoxyphene napsylate (100 rag)is equivalentin active drug to propoxyphene
HC1(65rag).
is more painful than a simple tooth extraction or a single quadrant flap procedure. Figure 3 depicts a study comparing aspirin in two clinical situations; with the less traumatic extraction pain 650 mg of aspirin appears to be more effective than with impaction pain (5). It is important to assess pain from several perspectives before deciding on the appropriate analgesic. The following criteria are suggested: (a) the extent of the surgical procedure; (b) the psychological make-up of the patient; (c) the patient's past experience with analgesics; and (d) the planned activity of the patient over the next 24 to 48 h. For most dental pain situations, the PA analgesics are extremely effective (6-8). There is reasonable evidence that several of the newer NSAIDs are at least as effective as the traditional codeine combinations (8). If a patient can tolerate aspirin-like drugs, then ibuprofen, ketoprofen, naproxen sodium, or meclofenamate sodium at their maximum indicated dose will provide substantial analgesia without the narcotic side effects (Fig. 4). If the clinical situation permits, pretreatment with these agents will enhance their therapeutic effect (9, 10). However, the clinician needs to be cautious about the theoretical possibility of prolonged surgical bleeding. In the published pretreatment studies, this was not a problem. If a patient cannot tolerate aspirin-like drugs, then the only PA
Vol. 16, No. 2, February 1990
Treating Acute Pain
89
TABLE 4. Currently available CAs (narcotic)* Drug Name
Trade Name
Chemical Derivation
DEA Schedule
Dosage (mg)
Morphine Hydromorphone Codeine Hydrocodone Oxycodone Meperidine Methadone Propoxyphene
MS Contin Dilaudid NA NA NA Demerol Dolophine Darvon HCI Darvon Napsylate Talwin NX Stadol Nubain Buprenex
O :)late O ~iate O )iate O ~iate O 3iate O )ioid O ~ioid O :)ioid Opioid Partial agonist Partial agonist Partial agonist Partial agonist
It II II II II II II IV IV IV Rxt Rx V
30-60 1-4 15-60 NA NA 50-100 5-10 32-65 50-100 50 NA NA NA
Pentazocine Butorphanol Nalbuphine Buprenorphine
First Pass Metabolism Up to Up to Up to Up to Up to Up to Up to Up to Up to Up to Up to Up to NA
Dosage for Dental Use in Combinations
90% 90% 50% 50% 50% 90% 50% 50% 50% 95% 95% 95%
NRJ" NR 15-60 5-10 2.5-10 NR NR 32-65 50-100 NR NA NA NA
9 Several of these d~gs are indicated as oral analgesics only in com~natlon wi~ PAs. Single e n v y Oral CAs are not recommended fOr dental pain. 1" NR. not recommended; NA. not a.pplKT,al~e. ,1:Rx means avmlable by pteso'lption without DEA sdledulw'~g.
TABLE 5. Analgesic combinations used in dentistry Constituents Trade Name Tylenol w/Codeine #2
PAs
CAs
DEA Other
Ill
--
COD 30
--
1 tablet every 4 - 6 h
III
ASA 325
COD 15
--
III
ASA 325
COD 30
--
#4 Synalgos DC
ASA 325 ASA 356
COD 60 DHCOD 16
-CAF
Vicodin, Lortab, Zydone
ACET 500
HCOD 5-7.5
--
Percodan
ASA 325
OXCOD 5
--
Percodan-Demi
ASA 325
OXCOD 2.5
--
Tylox
ACET 500
OXCOD 5
--
Percocet
ACET 325
OXCOD 5
--
Darvocet-N 50 Darvocet-N 100 Darvon W/A.SA.w (HCI salt) Talwin Compound
ACET 650 ACET 650 ASA 325 ASA 325
PROPOX 50 PROPOX 100 PROPOX 65 PENTAZ 12.5
-----
Talacen Fiorinal w/Codeine #1 #2 #3
ACET 650
PENTAZ 25
--
2-3 tablets every 4-6 h 1-2 tablets every 4-6 h Not recommended1" 1-2 tablets every 4-6 h 1-2 tablets every 4-6 h 1-2 tablets every 4-6 h 1-2 tablets every 4-6 h 1-2 tablets every 4-6 h 1-2 tablets every 4-6 h 1 tablet every 4 - 6 h 1 tablet every 4-6 h 1 tablet every 4-6 h 2 tablets every 4-6 h 1 tablet every 4 - 6 h
ASA 325 ASA 325 ASA 325
COD 7.5 COD 15 COD 30
CAF 40, BUT 50 CAF 40, BUT 50 CAF 40, BUT 50
Not recommendedll Not recommended Not recommended
#4 (Empracet w/Codeine) (Phenaphen w/Codeine) Phenaphen 650 w/Codeine Empirin w/Codeine #2 #3
COD 15
--
ACET 300
COD 30
--
ACET 300
COD 60
ACET 650
Schedule
2-3 tablets every 4-6 h 1-2 tablets every 4-6 h Not recommended1
#3
ACET ~ 300
Recommended Dosage
III Ill
III III III III II~t II~t II~t
IV IV IV IV IV III III Ill
9 ACET. acetaminophefl: ASA, aspire; COD. codeine, HCOD. hydrOCXXtOne: OXCOD. oxycodone; DHCOD. dihydrocodelne; PROPOX. propoxyphef~ napsylate: PENTAZ. pentazocine: CAF. caffeine: BUT. b~JtaJbltal t # 4 Preparations are not recommended because they contain inadequate amounts of the PAs. use two #3s. -t In g e t , rat. tt~ use of DEA Sctledule II drugs is discouraged unless clearly indicated w Several other Oarvon preDaratio~'ls exist, e.g. Darvon Compo~.r I', This table is not all :nctustve end the not recommended cetegor~ ~s strictty the authors opinion.
90
Cooper
Joumal of Endodontics
alternative is aeetaminophen. Although an effective analgesic, it is a weaker anti-inflammatory drug and a less effective
analgesic than the propionic acid derivatives ( 11 ). Depending on the clinical situation, the lack of a moodaltering effect by the PAs can be an advantage or disadvantage. Certainly, there are clinical situations when the pain is so 6.0-
/
EOOPER
E-
STUDY 17 / EXTRACTION PAIN / (N : 3 6 ) /
L,q v L,q W rr' 0
~J L~
w
L~.O
Z
uJ C~ L:J LL LL s >-
Z ud t--Z
( N : 7 ~ / "
8.0-
Z (3_
m
N=IIO 0
325 6 0 1300 ASPIRIN DOSE IN mg FIG 3. Dose-response data for aspinn demonstrating the effect of different intensities of pain.
intense or when the patient's reaction to pain is so exaggerated that a mood-altering drug would be appropriate. In this situation, the clinician is dealing both with the quantitative and qualitative aspects of analgesia and centrally acting, moodaltering drugs may be most appropriate. The crux of the matter is that when the clinician deems it appropriate, the CAs are the drugs of choice to "buzz" the pain away. In dentistry, it is most beneficial to utilize the maximum effect of the PA analgesic and use the minimal amount of CA analgesic that will accomplish this goal. Table 5 lists the available combination analgesics and suggests the most rational dosage. Once the mood-altering effect is not needed, it is appropriate to switch therapy to the single entity PA analgesic. In most clinical situations, the need for a CA analgesic should not exceed 1 to 2 days. The clinician needs to be familiar with identity and amount of each constituent in the combination. In order to maximize the PA, it often is necessary to take more than one tablet of the combination or to take an extra acetaminophen, aspirin, or ibuprofen tablet along with the combination tablet. For example, it is better to take two acetaminophen (300 mg) with codeine (15 mg) tablets (two #2s) than one #3 tablet. Likewise, either three #2s or two #3s would be more efficacious than one #4 tablet. There also may be some benefit to alternating between an acetaminophen-codeine combination and ibuprofen (or other NSAID) every 2 to 3 h. Although lacking direct clinical support, this regimen offers the theoretical advantages of the anti-inflammatory effects of the PA and the additive effects of the CA. When dental pain is mild to moderate, most patients do surprisingly well on the newer PA analgesics. Only when the pain becomes more intense or the psychological situation is such that a mood-altering drug is required are the CA anal-
3"
x PLACEBO o A600 Eg A 3 0 0 + 030
(n=39) ( n =4-4-)
-~ A 6 0 0
(n=41)
+
IBU
4- 0 6 0 4-00
(n=39)
(n=40)
LIJ 0
LILIJ IZ"
z
N=203 o
0
~
i
1
2
3
....
i
i
4
HOURS FIG 4. Time-effect curves for placebo, 600 mg of 8cetaminophen, 300 mg of acetaminophen + 30 mg of codeine, 600 mg of acetaminophen + 60 mg of codeine, and 400 mg of ibuprofen. Mean pain relief scores are plotted against time in hours.
Vol. 16, No. 2, February 1990
gesics indicated. Generally, the codeine or hydrocodone combinations are most effective and only on rare occasions would a DEA schedule II be necessary. An understanding of the etiology of pain and the mechanisms of actions of analgesics can truly lead to better clinical management of pain problems. In almost all dental pain situations, the patient's pain can be controlled with minimal risk and side effects from the therapy. Dr. Cooper is director of Pharmacology and Graduate Education, Departmerit of Oral Surgery and Pharmacolgy, University of Pennsylvama..(-;cho~ of Dental Medicine, Plliladelpl'lla, PA
Roferencea 1. Chapman CR. Bon~ca JJ. Current concepts--acute pain Kalamazoo, MI: Upjohn, A Scope Pul)hcat~n, 1983.
Treating Acute Pain
91
2. Cooper SA PharmacoE)gy and therapeutics in dentistry. 2nd ed.. Chap 21. St. Louis, CV Mosby, 1985 3. Fields HL. Pain New York: McGraw-HiU, 1987. 4. Melzack R (ed). Pain measurement and assessment. New York: Raven Press, 1985. 5. Cooper SA. Comparative analgesic efficaces of aspldn and acetan.noptlen. Arch Intern Meal 1981;141:282-5. 6. Cooper SA. The relative efficacy of ibuprofen in dental pain. Compen Contin Educ Dent 1986;7:578-97. 7. Forbes JA, Beaver Wl, White EH, White RW, Neilson GB, Shackle.ford RW. Diflunisal, a new oral analgesic with unusually long duration of action J Am Med Assoc 1982:248:2139-42. 8. Cooper SA. New penF~efa, y-actJng oral analgesics. Annu Rev Pharmacol Toxicol 1983;23:617 -47 9. Dionne RA, Cooper SA. Delaying the onset of postoperative dental pain by pretreatment with ibuprofen. Oral Surg Oral Meal Oral Patho11978;45:8516. 10. a,onne RA. Carnpceli P.A,Cooper SA, Ha, DL, Buckingham B. Suppression of postoperative pare by I~eOpecatlve administration of ibuprolen in comparison to placebo, acetam~nophen and acetaminophen plus codeine. J CSn Pharmacol 1983;23:37-43. 11. Cooper SA The relative eff~acy of ibuprofen in dental pain. Compen Contin Educ Dent 1986;7:578-97.
